Genetic Variant TARID:n.84G>A (chr6-133888899-C-T) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The ENST00000607033.5(TARID):n.84G>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.61 in 177,714 control chromosomes in the GnomAD database, including 34,706 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.60 ( 28638 hom., cov: 32)

Exomes 𝑓: 0.67 ( 6068 hom. )

Consequence

TARID
ENST00000607033.5 non_coding_transcript_exon

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.468

Variant links:

Genes affected

TARID (HGNC:50506): (TCF21 antisense RNA inducing promoter demethylation)

TARID links:

TCF21 (HGNC:11632): (transcription factor 21) TCF21 encodes a transcription factor of the basic helix-loop-helix family. The TCF21 product is mesoderm specific, and expressed in embryonic epicardium, mesenchyme-derived tissues of lung, gut, gonad, and both mesenchymal and glomerular epithelial cells in the kidney. Two transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Jul 2008]

TCF21 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.78).

BP6

Variant 6-133888899-C-T is Benign according to our data. Variant chr6-133888899-C-T is described in ClinVar as [Benign]. Clinvar id is 1278224.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.904 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
TARID	NR_109982.1 link	n.108G>A	non_coding_transcript_exon_variant	Exon 1 of 9
TCF21	NM_003206.4 link	c.-499C>T	upstream_gene_variant		ENST00000367882.5	NP_003197.2	O43680
TCF21	NM_198392.3 link	c.-499C>T	upstream_gene_variant			NP_938206.1	O43680

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TCF21	ENST00000367882.5 link	c.-499C>T		upstream_gene_variant		1	NM_003206.4	ENSP00000356857.5		O43680

Frequencies

GnomAD3 genomes

AF:

0.600

AC:

91141

AN:

151940

Hom.:

28620

Cov.:

show subpopulations

Gnomad AFR

AF:

0.430

Gnomad AMI

AF:

0.695

Gnomad AMR

AF:

0.729

Gnomad ASJ

AF:

0.642

Gnomad EAS

AF:

0.926

Gnomad SAS

AF:

0.715

Gnomad FIN

AF:

0.500

Gnomad MID

AF:

0.598

Gnomad NFE

AF:

0.653

Gnomad OTH

AF:

0.612

GnomAD4 exome

AF:

0.669

AC:

17152

AN:

25654

Hom.:

6068

Cov.:

AF XY:

0.673

AC XY:

8859

AN XY:

13156

show subpopulations

Gnomad4 AFR exome

AF:

0.424

Gnomad4 AMR exome

AF:

0.775

Gnomad4 ASJ exome

AF:

0.601

Gnomad4 EAS exome

AF:

0.934

Gnomad4 SAS exome

AF:

0.728

Gnomad4 FIN exome

AF:

0.493

Gnomad4 NFE exome

AF:

0.631

Gnomad4 OTH exome

AF:

0.606

GnomAD4 genome

AF:

0.600

AC:

91201

AN:

152060

Hom.:

28638

Cov.:

AF XY:

0.600

AC XY:

44560

AN XY:

74326

show subpopulations

Gnomad4 AFR

AF:

0.430

Gnomad4 AMR

AF:

0.729

Gnomad4 ASJ

AF:

0.642

Gnomad4 EAS

AF:

0.926

Gnomad4 SAS

AF:

0.715

Gnomad4 FIN

AF:

0.500

Gnomad4 NFE

AF:

0.653

Gnomad4 OTH

AF:

0.615

Alfa

AF:

0.657

Hom.:

43408

Bravo

AF:

0.612

Asia WGS

AF:

0.764

AC:

2656

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Nov 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

4.4

DANN

Benign

0.59

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over